The objectives of this project are two-fold. One is to develop, evaluate, and report the methodology and result for generation and monitoring techniques necessary for conducting chronic inhalation studies with ozone and NNK. The second is to characterize dose-response relationships, toxicity, and carcinogenic potential of ozone administered by inhalation to rats and mice in 2-year chronic studies while being given injections of NNK three times a week for 20 weeks. Animals will be exposed for 6 hours per day, 5 days per week for 2 years. At the end of two years, all animals will be given gross and microscopic histopathologic evaluations.